RESUMEN
Infections with multidrug-resistant gram-negative bacterial species are a great concern in clinics in Germany. By limiting therapeutic options dramatically, these bacteria pose a significant threat to patient health and cause extensive pressure on hygiene systems and patient management. In Germany, the recommendations on how to deal with these bacteria are called MRGN classification, using the terms 3MRGN and 4MRGN for bacteria resistant to three or four major classes of antibiotics. To be resistant to this large number of antibiotics and become classified as 3MRGN or 4MRGN, bacterial strains need to acquire multiple resistance mechanisms with beta-lactamases, especially carbapenemases, being the most important ones. According to established surveillance systems like national reporting systems, KISS or the National Reference Centre, multidrug-resistant bacteria are constantly on the rise in Germany. Although several novel therapeutic options have been approved recently, these bacteria represent a constant challenge and it may be necessary to discuss if the present hygiene recommendations need an update for an efficient and targeted prevention of transmission.
Asunto(s)
Farmacorresistencia Bacteriana Múltiple , Bacterias Gramnegativas , Infecciones por Bacterias Gramnegativas , Alemania , Humanos , Infecciones por Bacterias Gramnegativas/tratamiento farmacológico , Infecciones por Bacterias Gramnegativas/epidemiología , Bacterias Gramnegativas/efectos de los fármacos , Prevalencia , Antibacterianos/uso terapéuticoRESUMEN
Colistin is one of the last-resort antibiotics in treating infections caused by multidrug-resistant (MDR) pathogens. Unfortunately, the emergence of colistin-resistant gram-negative strains limit its clinical application. Here, we identify an FDA-approved drug, valnemulin (Val), exhibit a synergistic effect with colistin in eradicating both colistin-resistant and colistin-susceptible gram-negative pathogens both in vitro and in the mouse infection model. Furthermore, Val acts synergistically with colistin in eliminating intracellular bacteria in vitro. Functional studies and transcriptional analysis confirm that the combinational use of Val and colistin could cause membrane permeabilization, proton motive force dissipation, reduction in intracellular ATP level, and suppression in bacterial motility, which result in bacterial membrane disruption and finally cell death. Our findings reveal the potential of Val as a colistin adjuvant to combat MDR bacterial pathogens and treat recalcitrant infections.
Asunto(s)
Antibacterianos , Colistina , Diterpenos , Farmacorresistencia Bacteriana Múltiple , Bacterias Gramnegativas , Infecciones por Bacterias Gramnegativas , Pruebas de Sensibilidad Microbiana , Colistina/farmacología , Farmacorresistencia Bacteriana Múltiple/efectos de los fármacos , Animales , Antibacterianos/farmacología , Ratones , Diterpenos/farmacología , Infecciones por Bacterias Gramnegativas/tratamiento farmacológico , Infecciones por Bacterias Gramnegativas/microbiología , Bacterias Gramnegativas/efectos de los fármacos , Sinergismo Farmacológico , Femenino , HumanosRESUMEN
BACKGROUND: Antimicrobial resistance is a major global public health issue. Infections caused by resistant species are associated with higher mortality rates, longer hospital stays, medication failure, and rising medical costs. The World Health Organisation has declared multidrug resistance-associated infections as an epidemic of public health concern. OBJECTIVE: This study aimed to evaluate the antimicrobial resistance profile and associated factors of hospital-acquired Gram-negative bacterial pathogens among hospitalized patients in Northeast Ethiopia. MATERIALS AND METHODS: A health facility-based cross-sectional study was conducted among hospitalized patients from March 2021 to February 2022. About 810 clinical specimens were collected, transported, and processed from admitted patients following the standard bacteriological procedures. The clinical samples were inoculated onto blood agar, MacConkey agar, and chocolate agar. Furthermore, the species identification was done using gram reactions, colony morphology, and color and biochemical tests. Antimicrobial susceptibility tests, extended-spectrum beta-lactamase, and carbapenemase production were performed as per the clinical laboratory standard institute guidelines. For analysis, the information was entered into Epi-data and exported to SPSS. A P value of < 0.05 with a 95% confidence interval was considered as a statistically significant association. RESULTS: Out of 810 clinical specimens, 285/810 (35.2%) developed bacterial infections. From the isolated bacteria, E. coli was the predominant bacteria accounting for 78/285 (27.4%) followed by K. pneumoniae, 69/285(24.42%), whereas P. vulgaris accounted for the least, 7/285 (2.5%). Overall, 132/285 (46.3%) and 99/285 (34.7%) of culture-positive patients were infected by extended-spectrum beta-lactamase and carbapenemase-producing bacteria. The overall multidrug resistance rate of the isolated bacteria was 89.4%. The highest antibiotic resistance rates were detected for doxycycline (92.9%), amoxicillin-clavulanic acid (83.9%), and ampicillin (93%). The least antibiotic resistance rate was observed for meropenem at 41.1% and amikacin at 1.7%, respectively. CONCLUSIONS AND RECOMMENDATIONS: In the study area, significant health concerns include a range of hospital-acquired bacterial infections associated with elevated rates of multidrug resistance, Extended-spectrum beta-lactamase (ESBL), and carbapenemase-producing bacterial pathogens. Consequently, it is recommended to conduct drug-susceptibility testing of isolates and molecular detection at a national level to optimize antibiotic usage for treating prevalent bacterial infections in this area.
Asunto(s)
Antibacterianos , Infección Hospitalaria , Farmacorresistencia Bacteriana Múltiple , Bacterias Gramnegativas , Infecciones por Bacterias Gramnegativas , Pruebas de Sensibilidad Microbiana , Humanos , Etiopía/epidemiología , Estudios Transversales , Masculino , Femenino , Adulto , Persona de Mediana Edad , Antibacterianos/farmacología , Infección Hospitalaria/microbiología , Infección Hospitalaria/epidemiología , Bacterias Gramnegativas/efectos de los fármacos , Bacterias Gramnegativas/aislamiento & purificación , Bacterias Gramnegativas/clasificación , Bacterias Gramnegativas/genética , Adulto Joven , Adolescente , Infecciones por Bacterias Gramnegativas/microbiología , Infecciones por Bacterias Gramnegativas/epidemiología , Infecciones por Bacterias Gramnegativas/tratamiento farmacológico , Farmacorresistencia Bacteriana Múltiple/genética , beta-Lactamasas/genética , beta-Lactamasas/metabolismo , Anciano , Niño , Preescolar , Lactante , Hospitalización/estadística & datos numéricos , Proteínas Bacterianas/genética , Anciano de 80 o más AñosRESUMEN
BACKGROUND: Gram-negative bacteria resistant to carbapenems are also known as critical antimicrobial resistant organisms. Their emergence at Colonial War Memorial Hospital (CWMH), the largest hospital in Fiji, is a major clinical concern. This study was conducted to determine the knowledge, attitudes, and readiness of healthcare workers (HCW) at CWMH regarding management of patients with infections caused by critical antimicrobial resistant organisms. METHODS: A questionnaire was designed using a Likert scale to assess knowledge, attitudes, and readiness. Two cross-sectional studies were conducted, before and after the implementation of targeted educational activities which were informed by the pre-intervention study findings. RESULTS: A total of 393 and 420 HCW participated in the pre- and post-intervention studies, respectively. The majority of respondents were female (77.3%) and 18-34 years of age (67%). HCW professional roles included nurses (56.3%), doctors (31.6%), and laboratory personnel (12.2%). In the post-intervention study, significantly more HCW reported having received infection prevention and control (IPC) and antimicrobial resistance education and training (26.8% in pre to 45.5% in post intervention, p < 0.001). The majority of nurses and doctors (> 85% to ≥ 95%) were aware of how AMR organisms spread in healthcare settings and knew the IPC measures to prevent transmission of AMR infections including hand hygiene, standard and transmission-based precautions. Attitudes towards AMR were positive, with 84.2% pre intervention and 84.8% of HCW post intervention expressing their willingness to change their work environment to assist with AMR prevention. Perceived readiness to address the problem showed mixed results. Improvements in laboratory AMR surveillance data availability were noted (29.4-52.4%, p < 0001). Modest improvement in the hospital's capacity for outbreak response (44-51.9%, p = 0.01), and treatment of AMR infections (38.9-44.4%, p = 0.01) was reported. CONCLUSIONS: Our data revealed high levels of staff awareness and knowledge about AMR and IPC. However, readiness for outbreak response and treatment of critical AMR infections requires more attention. Improving AMR prevention and containment in CWMH will likely require sustained and multisectoral interventions with strong administrative commitment.
Asunto(s)
Conocimientos, Actitudes y Práctica en Salud , Personal de Salud , Humanos , Femenino , Masculino , Fiji , Adulto , Estudios Transversales , Personal de Salud/psicología , Adulto Joven , Encuestas y Cuestionarios , Adolescente , Control de Infecciones/métodos , Persona de Mediana Edad , Infección Hospitalaria/microbiología , Hospitales Militares , Actitud del Personal de Salud , Bacterias Gramnegativas/efectos de los fármacos , Infecciones por Bacterias GramnegativasRESUMEN
The body temperature of Warm-blooded hosts impedes and informs responses of bacteria accustomed to cooler environments. The second messenger c-di-GMP modulates bacterial behavior in response to diverse, yet largely undiscovered, stimuli. A long-standing debate persists regarding whether a local or a global c-di-GMP pool plays a critical role. Our research on a Stenotrophomonas maltophilia strain thriving at around 28°C, showcases BtsD as a thermosensor, diguanylate cyclase, and effector. It detects 37°C and diminishes c-di-GMP synthesis, resulting in a responsive sequence: the periplasmic c-di-GMP level is decreased, the N-terminal region of BtsD disengages from c-di-GMP, activates the two-component signal transduction system BtsKR, and amplifies sod1-3 transcription, thereby strengthening the bacterium's pathogenicity and adaptation during infections in 37°C warm Galleria mellonella larvae. This revelation of a single-protein c-di-GMP module introduces unrecognized dimensions to the functional and structural paradigms of c-di-GMP modules and reshapes our understanding of bacterial adaptation and pathogenicity in hosts with a body temperature around 37°C. Furthermore, the discovery of a periplasmic c-di-GMP pool governing BtsD-BtsK interactions supports the critical role of a local c-di-GMP pool.
Asunto(s)
Proteínas Bacterianas , GMP Cíclico , Infecciones por Bacterias Gramnegativas , Stenotrophomonas maltophilia , Stenotrophomonas maltophilia/metabolismo , GMP Cíclico/análogos & derivados , GMP Cíclico/metabolismo , Animales , Infecciones por Bacterias Gramnegativas/microbiología , Proteínas Bacterianas/metabolismo , Proteínas Bacterianas/genética , Transducción de Señal , Temperatura Corporal/fisiología , Regulación Bacteriana de la Expresión Génica , Liasas de Fósforo-Oxígeno/metabolismo , Liasas de Fósforo-Oxígeno/genéticaRESUMEN
Current pharmacotherapy remains futile in acute alveolar inflammation induced by Gram-negative bacteria (GNB), eliciting consequent respiratory failure. The release of lipid polysaccharides after antibiotic treatment and subsequent progress of proinflammatory cascade highlights the necessity to apply effective inflammation management simultaneously. This work describes modular self-assembling peptides for rapid anti-inflammatory programming (SPRAY) to form nanoparticles targeting macrophage specifically, having anti-inflammation and bactericidal functions synchronously. SPRAY nanoparticles accelerate the self-delivery process in macrophages via lysosomal membrane permeabilization, maintaining anti-inflammatory programming in macrophages with efficacy close to T helper 2 cytokines. By pulmonary deposition, SPRAY nanoparticles effectively suppress inflammatory infiltration and promote alveoli regeneration in murine aseptic acute lung injury. Moreover, SPRAY nanoparticles efficiently eradicate multidrug-resistant GNB in alveoli by disrupting bacterial membrane. The universal molecular design of SPRAY nanoparticles provides a robust and clinically unseen local strategy in reverse acute inflammation featured by a high accumulation of proinflammatory cellularity and drug-resistant bacteria.
Asunto(s)
Infecciones por Bacterias Gramnegativas , Nanopartículas , Animales , Ratones , Nanopartículas/química , Infecciones por Bacterias Gramnegativas/tratamiento farmacológico , Péptidos/química , Péptidos/farmacología , Péptidos/administración & dosificación , Bacterias Gramnegativas/efectos de los fármacos , Alveolos Pulmonares/efectos de los fármacos , Alveolos Pulmonares/patología , Alveolos Pulmonares/metabolismo , Administración por Inhalación , Antibacterianos/farmacología , Antibacterianos/química , Antibacterianos/administración & dosificación , Antiinflamatorios/farmacología , Antiinflamatorios/administración & dosificación , Antiinflamatorios/química , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Modelos Animales de Enfermedad , Inflamación/tratamiento farmacológico , Inflamación/patologíaRESUMEN
Aeromonas veronii is an opportunistic pathogen that poses great threat to aquaculture and human health, so there is an urgent need for green and efficient methods to deal with its infection. In this study, single and double gene deletion strains (AV-ΔaroA, AV-Δppk1 and AV-ΔaroA/ppk1) that can be stably inherited were constructed. Pathogenicity test showed that the toxicity of AV-ΔaroA and AV-ΔaroA/ppk1 was significantly lower compared to wild-type A. veronii. Biological characterization analysis revealed that the decrease in pathogenicity might be due to the declined growth, motility, biofilm formation abilities and the expression of virulence-related genes in mutants. Subsequently, we evaluated the efficacy of AV-ΔaroA/ppk1 as a live attenuated vaccine (LAV). Safety assessment experiments showed that AV-ΔaroA/ppk1 injected at a concentration of 3 × 107 CFU/mL was safe for C. carassius. The relative percentage survival of AV-ΔaroA/ppk1 was 67.85 %, significantly higher than that of the inactivated A. veronii, which had an RPS of 54.84 %. This improved protective effect was mainly attributed to the increased levels of A. veronii specific IgM antibody, enhanced alkaline phosphatase, lysozyme and superoxide dismutase activities, as well as higher expression levels of several immune related genes. Together, these findings deepen our understanding of the functional roles of aroA and ppk1 in A. veronii pathogenicity, provide a good candidate of LAV for A. veronii.
Asunto(s)
Aeromonas veronii , Vacunas Bacterianas , Enfermedades de los Peces , Infecciones por Bacterias Gramnegativas , Vacunas Atenuadas , Aeromonas veronii/patogenicidad , Aeromonas veronii/fisiología , Aeromonas veronii/inmunología , Vacunas Atenuadas/inmunología , Vacunas Bacterianas/inmunología , Infecciones por Bacterias Gramnegativas/veterinaria , Infecciones por Bacterias Gramnegativas/inmunología , Infecciones por Bacterias Gramnegativas/prevención & control , Enfermedades de los Peces/prevención & control , Enfermedades de los Peces/inmunología , Enfermedades de los Peces/microbiología , Animales , Virulencia , Proteínas Bacterianas/genética , Proteínas Bacterianas/inmunología , Carpas/inmunología , Eliminación de GenRESUMEN
Bacterial septicemia represents a significant disease affecting cultured grass carp culture, with the primary etiological agent identified as the Gram-negative bacterium Aeromonas veronii. In response to an outbreak of septicemia in Guangzhou, we developed a formaldehyde-inactivated vaccine against an A. veronii strain designated AV-GZ21-2. This strain exhibited high pathogenicity in experimental infections across at all developmental stages of grass carp. Mortality rates for grass carp weighing 15 ± 5 g ranged from 16 % to 92 % at exposure temperatures of 19 °C-34 °C, respectively. The median lethal dose (LD50) for grass carp groups weighing 15 ± 5 g, 60 ± 10 g, 150 ± 30 g and 500 ± 50 g were determined to be 1.43, 2.52, 4.65 and 7.12 × 107(CFU/mL), respectively. We investigated the inactivated vaccine in conbination with aluminum hydroxide gel (AV-AHG), Montanide ISA201VG (AV-201VG), and white oil (AV-WO) adjuvants. This study aimed to optimize inactivation conditions and identify the adjuvant that elicits the most robust immune response. The AV-GZ21-2 inactivated bacterial solution (AV),when combined with various adjuvants, was capable of inducing a strong specific immune response in grass carp. The relative percent survival (RPS) following a lethal challenge with AV-GZ21-2 were 94 % for AV-AHG, 88 % for AV-201VG, 84 % for AV-WO and 78 % for AV alone. The minimum immunization dose of the AV-AHG vaccine was determined to be 6.0 × 107 CFU per fish, providing immunity for a duration of six months with an immune protection level exceeding 75 %. Furthermore, the AV-AHG vaccine demonstrated significant protective efficacy against various epidemic isolates of A. veronii. Consequently, we developed an inactivated vaccine targeting a highly pathogenic strain of A. veronii, incorporating an aluminum hydroxide gel adjuvant, which resulted in high immune protection and a duration of immunity exceeding six months. These findings suggest that the AV-AHG vaccine holds substantial potential for industrial application.
Asunto(s)
Adyuvantes Inmunológicos , Aeromonas veronii , Vacunas Bacterianas , Carpas , Enfermedades de los Peces , Infecciones por Bacterias Gramnegativas , Vacunas de Productos Inactivados , Animales , Carpas/microbiología , Vacunas Bacterianas/inmunología , Vacunas Bacterianas/administración & dosificación , Vacunas de Productos Inactivados/inmunología , Vacunas de Productos Inactivados/administración & dosificación , Aeromonas veronii/inmunología , Enfermedades de los Peces/prevención & control , Enfermedades de los Peces/microbiología , Enfermedades de los Peces/inmunología , Infecciones por Bacterias Gramnegativas/prevención & control , Infecciones por Bacterias Gramnegativas/veterinaria , Infecciones por Bacterias Gramnegativas/inmunología , Virulencia , Adyuvantes Inmunológicos/administración & dosificación , Dosificación Letal Mediana , Temperatura , China/epidemiología , Hidróxido de Aluminio/administración & dosificaciónRESUMEN
BACKGROUND: Swine dysentery, caused by Brachyspira hyodysenteriae, is a severe pig disease. Resistance to tylosins is common and resistance to tiamulin has been reported since the 1990s. Still, dysentery is not notifiable to authorities. The disease therefore escapes control from an overall population perspective. In Sweden, a program that aimed to control dysentery at national level was initiated in 2020, mainly due to the unexpected diagnosis of tiamulin resistant Brachyspira hyodysenteriae in 2016. RESULTS: Through joint efforts of a network including farmers, government, animal health organisations and abattoirs it was concluded that outbreaks of dysentery had taken place in 25 herds between 2016 and 2019. By 1 January 2020, nine of these herds were still not declared free from the disease. From that date, the network decided that Brachyspira hyodysenteriae was to be cultured whenever dysentery could be suspected. Thus, 148, 157 and 124 herds were scrutinised for Brachyspira hyodysenteriae in 2020, 2021 and 2022, respectively, whereof five, three and two new herds were confirmed positive. By 31 December 2022, four herds were judged as impossible to sanitise. However, they posed no problem since they were identified by the network, pigs to and from these enterprises could be transported without jeopardising other herds. When Brachyspira hyodysenteriae was diagnosed in fattening herds purchasing growers, Brachyspira hyodysenteriae could not be detected in the delivering herds. That result, together with other observations, indicated that Brachyspira hyodysenteriae ought to be regarded as ubiquitous, although at a low level in healthy pigs. CONCLUSIONS: Eradication of dysentery contributed to substantial welfare and financial improvements in affected herds. Dysentery was controlled successfully at national level through the united efforts from competing stake holders, such as different abattoirs and animal health organisations. However, as Brachyspira hyodysenteriae was assumed to be ubiquitous, although at a low level in healthy pigs, the duration of the successful control of dysentery was concluded to only be transient. Without permanent monitoring for Brachyspira hyodysenteriae, the knowledge of the national status will rapidly decline to the level prior to the initiation of the control program.
Asunto(s)
Brachyspira hyodysenteriae , Disentería , Infecciones por Bacterias Gramnegativas , Enfermedades de los Porcinos , Animales , Suecia/epidemiología , Enfermedades de los Porcinos/microbiología , Enfermedades de los Porcinos/epidemiología , Enfermedades de los Porcinos/prevención & control , Porcinos , Infecciones por Bacterias Gramnegativas/veterinaria , Infecciones por Bacterias Gramnegativas/epidemiología , Infecciones por Bacterias Gramnegativas/microbiología , Disentería/veterinaria , Disentería/epidemiología , Disentería/microbiología , Brotes de Enfermedades/veterinariaRESUMEN
Antimicrobial resistance is currently recognized as an urgent concern against public health in worldwide. Carbapenem-resistant (CR) Gram-negative bacteria, such as Enterobacterales, Pseudomonas aeruginosa and Acinetobacter baumannii are listed as critical pathogens which are widely spread and can cause severe and often deadly infections in WHO guidance. Cefiderocol (Fetroja®), a novel and first siderophore cephalosporin, was approved for the infections caused by these problematic CR Gram-negative bacteria in Japan on November 30, 2023. Cefiderocol has unique mechanisms to be incorporated into bacterial cells using bacterial iron transportation system and to be highly stable against most ß-lactamases, which lead to promising antibacterial activity against these Gram-negative bacteria including CR strains in vitro. In CREDIBLE-CR Ph3 trial, cefiderocol showed the good efficacy and safety for patients with CR Gram-negative bacteria. In APEKS-cUTI and APEKS-NP trials, cefiderocol showed non-inferiority and suggested superiority to imipenem/cilastatin in complicated urinary tract infection (cUTI) patients, and non-inferiority to high dose of meropemen in pneumonia patients, respectively. Cefiderocol is expected to be an optimal treatment for CR Gram-negative infections with limited treatment options and would be an important drug to combat the threat of CR bacteria.
Asunto(s)
Antibacterianos , Carbapenémicos , Cefiderocol , Cefalosporinas , Infecciones por Bacterias Gramnegativas , Sideróforos , Humanos , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Carbapenémicos/farmacología , Carbapenémicos/uso terapéutico , Cefiderocol/farmacología , Cefiderocol/uso terapéutico , Cefalosporinas/farmacología , Cefalosporinas/uso terapéutico , Farmacorresistencia Bacteriana , Bacterias Gramnegativas/efectos de los fármacos , Infecciones por Bacterias Gramnegativas/tratamiento farmacológico , Sideróforos/farmacologíaRESUMEN
PURPOSE OF REVIEW: This review describes the latest information in the management of bloodstream infections caused by multidrug-resistant Gram-negative bacilli (MDRGNB) in critically ill patients. RECENT FINDINGS: The prevalence of bloodstream infections due to MDRGNB is high, and they pose a significant risk in critically ill patients. Recently, novel antimicrobial agents, including new ß-lactam/ß-lactamase inhibitor combinations and cefiderocol, have been introduced for treating these infections. Concurrently, updated guidelines have been issued to aid in treatment decisions. Prompt diagnosis and identification of resistance patterns are crucial for initiating effective antibiotic therapy. Current studies, especially with observational design, and with limited sample sizes and patients with bacteremia, suggest that the use of these new antibiotics is associated with improved outcomes in critically ill patients with MDRGNB bloodstream infections. SUMMARY: For critically ill patients with bloodstream infections caused by MDRGNB, the use of newly developed antibiotics is recommended based on limited observational evidence. Further randomized clinical trials are necessary to determine the most effective antimicrobial therapies among the available options.
Asunto(s)
Antibacterianos , Bacteriemia , Enfermedad Crítica , Farmacorresistencia Bacteriana Múltiple , Infecciones por Bacterias Gramnegativas , Humanos , Antibacterianos/uso terapéutico , Bacteriemia/tratamiento farmacológico , Bacteriemia/microbiología , Infecciones por Bacterias Gramnegativas/tratamiento farmacológico , Guías de Práctica Clínica como Asunto , Bacterias Gramnegativas/efectos de los fármacos , Unidades de Cuidados IntensivosRESUMEN
Mammalian interleukin-22 (IL-22) attenuates organismal injury by inhibiting reactive oxygen species (ROS) and impeding the NLRP3 inflammasome activation. However, the role of fish IL-22 in this process remains unclear. We characterized MaIL-22, an IL-22 homolog in blunt snout bream (Megalobrama amblycephala). Despite its low sequence identity, it shares conserved structures and close evolutionary relationships with other teleost IL-22s. Furthermore, Aeromonas hydrophila (A. hydrophila) infection leads to tissue injury in M. amblycephala immune organs and concomitantly altered Mail-22 mRNA expression, suggesting that MaIL-22 was involved in the antimicrobial immune response. To explore MaIL-22's biological functions, we produced recombinant MaIL-22 (rMaIL-22) protein and demonstrated it significantly enhanced the survival of M. amblycephala post-A. hydrophila infection. To unravel its protective mechanisms, we explored the ROS/NLRP3 inflammasome axis and its downstream signaling responses. The results showed that rMaIL-22 treatment significantly elevated antioxidant enzyme (T-SOD, CAT and GSH-PX) activities to inhibit MDA activity and scavenge ROS in visceral tissues. Meanwhile, rMaIL-22 impeded the activation of NLRP3 inflammasome by suppressing NLRP3 protein and mRNA expression. This indicated that rMaIL-22 contributed to inhibit A. hydrophila-induced activation of the ROS/NLRP3 inflammasome axis. Consistent with these findings, rMaIL-22 treatment attenuated the expression of proinflammatory cytokines (il-1ß, tnf-α and il-6) and proapoptotic genes (caspase-3 and caspase-8) while promoting antiapoptotic genes (bcl-2b and mcl-1a) expression, ultimately mitigating tissue injury in visceral tissues. In conclusion, our research underscores MaIL-22's key role in microbial immune regulation, offering insights for developing IL-22-targeted therapies and breeding programs.
Asunto(s)
Aeromonas hydrophila , Apoptosis , Enfermedades de los Peces , Infecciones por Bacterias Gramnegativas , Inflamasomas , Inflamación , Interleucina-22 , Interleucinas , Proteína con Dominio Pirina 3 de la Familia NLR , Especies Reactivas de Oxígeno , Animales , Aeromonas hydrophila/inmunología , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Inflamasomas/metabolismo , Inflamasomas/inmunología , Apoptosis/efectos de los fármacos , Infecciones por Bacterias Gramnegativas/inmunología , Especies Reactivas de Oxígeno/metabolismo , Interleucinas/metabolismo , Interleucinas/inmunología , Enfermedades de los Peces/inmunología , Enfermedades de los Peces/microbiología , Inflamación/inmunología , Proteínas de Peces/metabolismo , Proteínas de Peces/inmunología , Proteínas de Peces/genética , Cyprinidae/inmunología , Cyprinidae/metabolismo , Transducción de SeñalRESUMEN
BACKGROUND: Veno-venous extracorporeal membrane oxygenation (V-V ECMO) is a rapidly expanding life-support technique worldwide. The most common indications are severe hypoxemia and/or hypercapnia, unresponsive to conventional treatments, primarily in cases of acute respiratory distress syndrome. Concerning potential contraindications, there is no mention of microbiological history, especially related to multi-drug resistant (MDR) bacteria isolated before V-V ECMO placement. Our study aims to investigate: (i) the prevalence and incidence of MDR Gram-negative (GN) bacteria in a cohort of V-V ECMOs; (ii) the risk of 1-year mortality, especially in the case of predetected MDR GN bacteria; and (iii) the impact of annual hospital V-V ECMO volume on the probability of acquiring MDR GN bacteria. METHODS: All consecutive adults admitted to the Intensive Care Units of 5 Italian university-affiliated hospitals and requiring V-V ECMO were screened. Exclusion criteria were age < 18 years, pregnancy, veno-arterial or mixed ECMO-configuration, incomplete records, survival < 24 h after V-V ECMO. A standard protocol of microbiological surveillance was applied and MDR profiles were identified using in vitro susceptibility tests. Cox-proportional hazards models were applied for investigating mortality. RESULTS: Two hundred and seventy-nine V-V ECMO patients (72% male) were enrolled. The overall MDR GN bacteria percentage was 50%: 21% (n.59) detected before and 29% (n.80) after V-V ECMO placement. The overall 1-year mortality was 42%, with a higher risk observed in predetected patients (aHR 2.14 [1.33-3.47], p value 0.002), while not in 'V-V ECMO-acquired MDR GN bacteria' group (aHR 1.51 [0.94-2.42], p value 0.090), as compared to 'non-MDR GN bacteria' group (reference). Same findings were found considering only infections. A larger annual hospital V-V ECMO volume was associated with a lower probability of acquiring MDR GN bacteria during V-V ECMO course (aOR 0.91 [0.86-0.97], p value 0.002). CONCLUSIONS: 21% of MDR GN bacteria were detected before; while 29% after V-V ECMO connection. A history of MDR GN bacteria, isolated before V-V ECMO, was an independent risk factor for mortality. The annual hospital V-V ECMO volume affected the probability of acquiring MDR GN bacteria. Trial Registration ClinicalTrial.gov Registration Number NCTNCT06199141, date 12.26.2023.
Asunto(s)
Farmacorresistencia Bacteriana Múltiple , Oxigenación por Membrana Extracorpórea , Bacterias Gramnegativas , Humanos , Oxigenación por Membrana Extracorpórea/métodos , Oxigenación por Membrana Extracorpórea/estadística & datos numéricos , Femenino , Masculino , Estudios Retrospectivos , Persona de Mediana Edad , Adulto , Bacterias Gramnegativas/efectos de los fármacos , Italia/epidemiología , Infecciones por Bacterias Gramnegativas/tratamiento farmacológico , Infecciones por Bacterias Gramnegativas/mortalidad , AncianoRESUMEN
BACKGROUND: Antibiotic resistance among Gram-negative bacteria in intensive care units (ICUs) is linked with high morbidity and mortality in patients. In this study, we estimated the therapeutic coverage of various antibiotics, focusing on cefiderocol and comparators, administered empirically against an infection of unknown origin in the ICU. METHODS: In the ARTEMIS surveillance study, susceptibilities of 624 Italian Gram-negative isolates to amikacin, aztreonam-avibactam, cefiderocol, ceftazidime-avibactam, ceftolozane-tazobactam, colistin, imipenem-relebactam, meropenem, and meropenem-vaborbactam were tested by broth microdilution, and results were interpreted by European Committee on Antimicrobial Susceptibility Testing breakpoints. The susceptibility rates from the ARTEMIS study were extrapolated to Gram-negative isolates obtained from 5,774 patients in Italian ICUs in 2021. The sum of the predicted susceptibilities of individual pathogens represented the overall likelihood of in vitro activity of each antibiotic as early targeted therapy for ICU patients. RESULTS: A total of 624 Italian Gram-negative isolates included 206 Pseudomonas aeruginosa, 138 Acinetobacter baumannii, 187 Klebsiella pneumoniae, and 93 Escherichia coli. Against A. baumannii, K. pneumoniae, P. aeruginosa, and E. coli, the overall susceptibility rates for cefiderocol were 87.7%, 96.8%, 99%, and 100%, respectively; and for comparator agents, 8.7-96.4%, 25.7-100%, 73.3-100%, and 89.2-100%, respectively. Among the subset of meropenem-resistant isolates, susceptibility rates of A. baumannii, K. pneumoniae, and P. aeruginosa to cefiderocol were 86.4%, 96.2% and 100%, respectively. Corresponding susceptibility rates to comparator agents were 0-96.8%, 0-100%, and 6.4-100%, respectively. There were no meropenem-resistant isolates of E. coli. The extrapolation of data to isolates from Italian ICUs showed that the highest likelihood of therapeutic coverage, both overall and among meropenem-resistant isolates, was reported for colistin (96.8% and 72.2%, respectively) and cefiderocol (95.7% and 71.4%, respectively). All other antibiotics were associated with a likelihood below 73% overall and between 0% and 41.4% for meropenem-resistant isolates. CONCLUSIONS: Based on confirmed susceptibility rates and reported ICU prevalence of multiple Gram-negative species, cefiderocol showed a higher predicted therapeutic coverage and utility in ICUs compared with comparator beta-lactam-beta-lactamase inhibitor antibiotics. Cefiderocol may be a promising early treatment option for patients at high risk of carbapenem-resistant Gram-negative bacterial infections in the ICU.
Asunto(s)
Antibacterianos , Carbapenémicos , Bacterias Gramnegativas , Infecciones por Bacterias Gramnegativas , Unidades de Cuidados Intensivos , Pruebas de Sensibilidad Microbiana , Humanos , Italia/epidemiología , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Infecciones por Bacterias Gramnegativas/tratamiento farmacológico , Infecciones por Bacterias Gramnegativas/microbiología , Infecciones por Bacterias Gramnegativas/epidemiología , Carbapenémicos/farmacología , Carbapenémicos/uso terapéutico , Bacterias Gramnegativas/efectos de los fármacos , Cefalosporinas/farmacología , Cefalosporinas/uso terapéutico , Klebsiella pneumoniae/efectos de los fármacos , Pseudomonas aeruginosa/efectos de los fármacos , Acinetobacter baumannii/efectos de los fármacos , Meropenem/farmacología , Meropenem/uso terapéutico , Farmacorresistencia Bacteriana Múltiple , Cefiderocol , Colistina/farmacología , Colistina/uso terapéuticoRESUMEN
BACKGROUND: The study aimed to compare polymyxin B with colistimethate sodium (CMS) regarding neurotoxicity, nephrotoxicity and 30-day mortality in patients with MDR Gram-negatives. METHODS: All adult patients who received polymyxin B or CMS for at least 24 h for the treatment of MDR microorganisms were evaluated retrospectively. RESULTS: Among 413 initially screened patients, 147 patients who were conscious and able to express their symptoms were included in the neurotoxicity analysis. 13 of 77 patients with polymyxin B and 1 of 70 with CMS had neurotoxic adverse events, mainly paresthesias. All events were reversible after drug discontinuation. Among 290 patients included in nephrotoxicity analysis, the incidence of acute kidney injury (AKI) was 44.7% and 40.0% for polymyxin B and CMS, respectively (p = 0.425). AKI occurred two days earlier with colistin than polymyxin B without statistical significance (median (IQR): 5 (3-11) vs. 7 (3-12), respectively, p = 0.701). Polymyxin therapy was withdrawn in 41.1% of patients after AKI occurred and CMS was more frequently withdrawn than polymyxin B (p = 0.025). AKI was reversible in 91.6% of patients with CMS and 79% with polymyxin B after the drug withdrawal. Older age, higher baseline serum creatinine and the use of at least two nephrotoxic drugs were independent factors associated with AKI (OR 1.05, p < 0.001; OR 2.99, p = 0.022 and OR 2.45, p = 0.006, respectively). Septic shock, mechanical ventilation, presence of a central venous catheter and Charlson comorbidity index (OR 2.13, p = 0.004; OR 3.37, p < 0.001; OR 2.47, p = 0.004 and OR 1.21, p p < 0.001, respectively) were the independent predictors of mortality. The type of polymyxin was not related to mortality. CONCLUSIONS: Neurotoxicity is a relatively common adverse event that leads to drug withdrawal during polymyxins, particularly polymyxin B. Nephrotoxicity is very common during polymyxin therapy and the two polymyxins display similar nephrotoxic events with high reversibility rates after drug withdrawal. Close monitoring of AKI is crucial during polymyxin therapy, particularly, for elderly patients, patients who have high baseline creatinine, and using other nephrotoxic drugs.
Asunto(s)
Lesión Renal Aguda , Antibacterianos , Colistina , Polimixina B , Humanos , Colistina/efectos adversos , Colistina/análogos & derivados , Polimixina B/efectos adversos , Polimixina B/uso terapéutico , Masculino , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Anciano , Antibacterianos/efectos adversos , Lesión Renal Aguda/inducido químicamente , Infecciones por Bacterias Gramnegativas/tratamiento farmacológico , Adulto , Farmacorresistencia Bacteriana Múltiple , Anciano de 80 o más Años , Síndromes de Neurotoxicidad/etiología , Síndromes de Neurotoxicidad/epidemiologíaRESUMEN
RATIONALE: Shewanella algae are Gram-negative bacteria that are widely found in aquatic habitats and rarely cause lung infections in inland areas. PATIENT CONCERNS: Cough with light-yellow phlegm for 2 weeks. DIAGNOSES: The final diagnosis was bacterial pneumonia. INTERVENTIONS: The patient was treated with ceftazidime (2 g, every 12 h) for 1 week. OUTCOMES: The patient's lung infection improved and he was discharged. LESSONS: This case highlights a rare occurrence of lung infection caused by Shewanella algae in elderly Tibetan men residing in non-marine environments.
Asunto(s)
Antibacterianos , Infecciones por Bacterias Gramnegativas , Neumonía Bacteriana , Shewanella , Humanos , Masculino , Shewanella/aislamiento & purificación , Infecciones por Bacterias Gramnegativas/diagnóstico , Infecciones por Bacterias Gramnegativas/tratamiento farmacológico , Infecciones por Bacterias Gramnegativas/microbiología , Neumonía Bacteriana/microbiología , Neumonía Bacteriana/tratamiento farmacológico , Neumonía Bacteriana/diagnóstico , Neumonía Bacteriana/complicaciones , Antibacterianos/uso terapéutico , Tibet , Ceftazidima/uso terapéutico , Ceftazidima/administración & dosificación , AncianoRESUMEN
Aeromonas hydrophila (A. hydrophila) is one of the most pathogenic disease-causing bacteria, and causes massive death of animals including fish. Thus, strategies are being sought to ameliorate the impact of A. hydrophila. In this study, we have evaluated the ameliorative potential of dietary Lactobacillus delbrueckii (L. delbrueckii). The fishes were divided into the control group, an A. hydrophila group (A. hydrophila), and an L. delbrueckii group (A. hydrophila + 1*107 CFU/g L. delbrueckii). The results showed that A. hydrophila increased reactive oxygen species (ROS) content. However, dietary supplementation with L. delbrueckii prevented oxidative damage caused by elevated levels of ROS. The toxic effects of A. hydrophila on superoxide dismutase (SOD) activity, glutathione-S-transferase (GST), glutathione peroxidase (GPx), and glutathione reductase (GR), along with the levels of glutathione (GSH), were mitigated by dietary L. delbrueckii (P < 0.05). Also, Dietary L. delbrueckii induced the expression of antioxidant-related genes (sod, cat, gpx, gst, NF-E2-related factor 2 (nrf2), Kelch-like-ECH-and associated protein 1a (keap1a)) in the intestine of fish (P < 0.05). Furthermore, L. delbrueckii increased A. hydrophila-induced lysozyme, ACP, C3, and C4 decline. The mRNA expression levels of interleukin 1ß (il-1ß), interleukin 8 (il-8), tumour necrosis factor α (tnf-α), and nuclear transcription factor-κB p65 (nf-κb p65) were significantly elevated by A. hydrophila. In contrast, the relative mRNA expression levels of inhibitor factor κBα (iκbα) in the intestine were decreased by A. hydrophila (P < 0.05). However, L. delbrueckii prevented A. hydrophila-induced the relative mRNA expression changes. These present results demonstrate that dietary L. delbrueckii alleviated A. hydrophila-induced oxidative stress, immunosuppression, inflammation, and apoptosis in common Cyprinus carpio.
Asunto(s)
Aeromonas hydrophila , Carpas , Enfermedades de los Peces , Infecciones por Bacterias Gramnegativas , Lactobacillus delbrueckii , Factor 2 Relacionado con NF-E2 , FN-kappa B , Estrés Oxidativo , Transducción de Señal , Animales , Carpas/microbiología , Estrés Oxidativo/efectos de los fármacos , Factor 2 Relacionado con NF-E2/metabolismo , Enfermedades de los Peces/microbiología , Enfermedades de los Peces/prevención & control , Infecciones por Bacterias Gramnegativas/veterinaria , FN-kappa B/metabolismo , Inflamación , Probióticos/farmacología , Proteínas de Peces/metabolismoRESUMEN
BACKGROUND: Cupriavidus gilardii is an aerobic, gram-negative, motile, glucose-nonfermenting bacillus, first described in 1999. Typically, it exhibits low pathogenicity in humans, causing opportunistic infections primarily in individuals with compromised immune systems. This bacterium has been also found in various environmental sources such as plants and contaminated soils. Notably, there have been no documented cases of C. gilardii infections in animals. CASE PRESENTATION: This case report outlines a bovine neonatal diarrhea outbreak that occurred in Northern Greece, during which C. gilardii was isolated. Faecal samples from 5-day-old calves were collected and transported to the laboratory for further examination. Bacterial culture and next generation sequencing techniques were employed to confirm the presence of this bacterium in the samples. Following the isolation and identification of C. gilardii from the samples, an autogenous vaccine was produced and administered to the cows within the farm. Subsequent to vaccination, a progressive reduction in calf diarrhea and deaths was observed, leading to their eventual complete resolution. To the best of our knowledge, this represents the first documentation of C. gilardii isolation from cases of bovine neonatal diarrhea. CONCLUSION: This case report presents the first isolation case of C. gilardii from animal samples and more specifically from calf faecal samples. It represents an important observation, providing evidence that this opportunistic human pathogen could contribute to clinical symptoms in animals.
Asunto(s)
Animales Recién Nacidos , Enfermedades de los Bovinos , Cupriavidus , Diarrea , Brotes de Enfermedades , Heces , Infecciones por Bacterias Gramnegativas , Animales , Bovinos , Diarrea/veterinaria , Diarrea/microbiología , Diarrea/epidemiología , Brotes de Enfermedades/veterinaria , Enfermedades de los Bovinos/microbiología , Enfermedades de los Bovinos/epidemiología , Heces/microbiología , Infecciones por Bacterias Gramnegativas/veterinaria , Infecciones por Bacterias Gramnegativas/epidemiología , Infecciones por Bacterias Gramnegativas/microbiología , Cupriavidus/aislamiento & purificación , Cupriavidus/genética , Grecia/epidemiologíaRESUMEN
Aeromonas salmonicida is a common pathogenic bacterial species found in both freshwater and marine fish, leading to significant economic losses in the aquaculture industry. YidC is an accessory to SecYEG and is essential for the SecYEG transporter to insert into the bacterial membrane. However, the roles of the yidC gene on the host immune response remain unclear. Here, we compared the pathogenicity of yidC gene-deleted (ΔyidC) strain and wild-type (SRW-OG1) strain of mesophilic A. salmonicida to Orange-spotted grouper (Epinephelus coioides), and explored the impacts of yidC gene on the immune response of E. coioides to mesophilic A. salmonicida infection by using Red/ET recombineering. In this study, the E. coioides in the Secondary infected group had a 53.9 % higher survival rate than those in the Primary infected group. In addition, the adhesion ability of ΔyidC strain decreased by about 83.36 % compared with that of the wild-type (SRW-OG1) strain. Further comparison of the biological phenotype of SRW-OG1 and ΔyidC revealed that this yidC gene could regulate the expression of genes related to iron metabolism and have no effect on bacterial growth under the limited iron concentration. In the low concentration of Fe3+ and Fe2+ environment, SRW-OG1 can obtain iron ions by regulating yidC. Based on the above results, yidC gene contributed to the pathogenicity of mesophilic A. salmonicida to E. coioides, deletion of yidC gene promoted the inflammation and immune response of E. coioides to mesophilic A. salmonicida infection.
Asunto(s)
Aeromonas salmonicida , Proteínas Bacterianas , Enfermedades de los Peces , Infecciones por Bacterias Gramnegativas , Animales , Enfermedades de los Peces/inmunología , Enfermedades de los Peces/microbiología , Virulencia , Infecciones por Bacterias Gramnegativas/inmunología , Infecciones por Bacterias Gramnegativas/veterinaria , Infecciones por Bacterias Gramnegativas/microbiología , Aeromonas salmonicida/fisiología , Aeromonas salmonicida/patogenicidad , Proteínas Bacterianas/genética , Lubina/inmunología , Lubina/genética , Inmunidad Innata/genéticaRESUMEN
Aeromonas hydrophila, the pathogen that is the causative agent of motile Aeromonas septicemia (MAS) disease, commonly attacks freshwater fishes, including yellow catfish (Pelteobagrus fulvidraco). Although the kidney is one of the most important organs involved in immunity in fish, its role in disease progression has not been fully elucidated. Understanding the cellular composition and innate immune regulation mechanisms of the kidney of yellow catfish is important for the treatment of MAS. In this study, single-cell RNA sequencing (scRNA-seq) was performed on the kidney of hybrid yellow catfish (Pelteobagrus fulvidraco â × Pelteobagrus vachelli â) after A. hydrophila infection. Nine types of kidney cells were identified using marker genes, and a transcription module of marker genes in the main immune cells of hybrid yellow catfish kidney tissue was constructed using in-situ hybridization. In addition, the single-cell transcriptome data showed that the differentially expressed genes of macrophages were primarily enriched in the Toll-like receptor and Nod-like receptor signaling pathways. The expression levels of genes involved in these pathways were upregulated in macrophages following A. hydrophila infection. Transmission electron microscopy and TUNEL analysis revealed the cellular characteristics of macrophages before and after A. hydrophila infection. These data provide empirical support for in-depth research on the role of the kidney in the innate immune response of hybrid yellow catfish.